Efficacy and Safety of Extended-Release Niacin/ Laropiprant/Simvastatin Tablets in Participants With Hypercholesterolemia or Mixed Dyslipidemia (MK-0524B-143)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 3

Conditions: Mixed Dyslipidemia; Primary Hypercholesterolemia

Treatments: Drug: SIM-matching placebo; Drug: ER niacin/laropiprant (ERN/LRPT); Drug: Placebo Run-In; Drug: Simvastatin (SIM); Drug: ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01335997

2011-001007-12 (EudraCT Number)

0524B-143

Details and patient eligibility

About

This study is being done to find out if tablets containing extended release (ER) niacin, laropiprant, and simvastatin (ERN/LRPT/SIM) are as effective as tablets containing ER niacin and laropiprant taken with simvastatin tablets (ERN/LRPT + SIM) for lowering high cholesterol and high lipid levels in the blood. The primary hypothesis is that ERN/LRPT/SIM 2 g /20 mg is equivalent to ERN/LRPT 2 g coadministered with simvastatin 20 mg in reducing low-density lipoprotein cholestrol (LDL-C).

Enrollment: 1,139 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has a history of primary hypercholesterolemia or mixed dyslipidemia and meets LDL-C and triglyceride criteria.
• Is high risk coronary heart disease (CHD) and has LDL-C ≤190 mg/dL (≤4.91 mmol/L).
• Is not high risk CHD and has LDL-C ≤240 mg/dL (≤6.21 mmol/L).

Exclusion criteria

• Is pregnant or breast-feeding, or expecting to conceive or donate eggs or sperm during the study.
• Has a history of malignancy within ≤5 years, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• Consumes more than 3 alcoholic drinks per day (14 per week).
• Is a high risk CHD patient on lipid modifying therapy (LMT).
• Is on any LMT with equivalent or greater LDL-C-lowering efficacy than simvastatin 40 mg.
• Has Type 1 or Type 2 diabetes mellitus that is poorly controlled, or on statin therapy.
• Currently engages in vigorous exercise or is on an aggressive diet regimen.
• Has uncontrolled endocrine or metabolic disease, uncontrolled gout, kidney or hepatic disease, heart failure, recent peptic ulcer disease, hypersensitivity or allergic reaction to niacin or simvastatin, recent heart attack, stroke or heart surgery.
• Is human immunodeficiency virus (HIV) positive.
• Has taken niacin >50 mg/day, bile-acid sequestrants, 3-hydroxy-3-methylglutaryl-coenzyme A(HMG-CoA) reductase inhibitors, ezetimibe, Cholestin™ [red yeast rice] and other red yeast products within 6 weeks, or fibrates within 8 weeks of randomization visit (Visit 3).

Note: Fish oils, phytosterol margarines and other non-prescribed therapies are allowed provided participant has been on a stable dose for 6 weeks prior to Visit 2 and agrees to remain on this dose for the duration of the study.

• Is currently receiving cyclical hormonal contraceptives or intermittent use of hormone replacement therapies (HRTs) (e.g., estradiol, medroxyprogesterone, progesterone). Note: Participants who have been on a stable dose of non-cyclical HRT or hormonal contraceptive for greater than 6 weeks prior to Visit 1 are eligible if they agree to remain on the same regimen for the duration of the study.
• Is taking prohibited medications such as systemic corticosteroids, potent inhibitors of Cytochrome P450 3A4 (CYP3A4), cyclosporine, danazol, or fusidic acid.
• Consumes >1 quart of grapefruit juice/day.
• Requires warfarin treatment and has not been on a stable dose with a stable International Normalized Ratio (INR) for at least 6 weeks prior to Visit 1.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

1,139 participants in 2 patient groups

ERN/LRPT/SIM → ERN/LRPT+SIM

Experimental group

Description:

Weeks 0-4 (Period 1): Participants will take ERN/LRPT/SIM 1 g/10 mg and SIM-matching placebo tablets daily; Weeks 5-12 (Period 2): Participants will be advanced to ERN/LRPT/SIM 2 g/20 mg and SIM-matching placebo tablets daily; Weeks 13-20 (Period III): Participants will crossover to ERN/LRPT 2 g + SIM 20 mg coadministration treatment.

Treatment:

Drug: ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)

Drug: Simvastatin (SIM)

Drug: Placebo Run-In

Drug: ER niacin/laropiprant (ERN/LRPT)

Drug: SIM-matching placebo

ERN/LRPT+SIM → ERN/LRPT/SIM

Active Comparator group

Description:

Weeks 0-4 (Period I): Participants will take ERN/LRPT co-administered with SIM (ERN/LRPT 1g + SIM 10 mg tablets) daily; Weeks 5-12 (Period II): Participants will be advanced to ERN/LRPT 2 g + SIM 20 mg daily; Weeks 13-20 (Period III): Participants will crossover to the ERN/LRPT/SIM 2 g/20 mg combination treatment and SIM-matching placebo tablets.

Treatment:

Drug: ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)

Drug: Simvastatin (SIM)

Drug: Placebo Run-In

Drug: ER niacin/laropiprant (ERN/LRPT)

Drug: SIM-matching placebo